A palm-worn device to quantify rigidity in Parkinson's disease.

BACKGROUND: Parkinsonian rigidity is identified on clinical examination as resistance to passive movement. Measurement of rigidity commonly relies on ordinal rating scales (MDS-UPDRS), however instrumented objective measures may provide greater mechanistic insight. NEW METHOD: We present a palm-worn instrument to objectively quantify rigidity on a continuous scale. The device employs a miniature motor to flex the third digit of the hand about the metacarpophalangeal joint whilst transducers record flexion/extension forces. We aim to determine congruence with the MDS-UPDRS, investigate sensitivity to the impact of deep brain stimulation (DBS) and contralateral movement, and make comparisons with healthy individuals. Eight participants with Parkinson's disease underwent evaluation during conditions: on and off DBS, and with and without contralateral limb movement to activate rigidity. During each DBS condition, wash-in/out effects were tracked using both our instrument and two blinded clinical raters. Sixteen healthy volunteers (age-matched/young) served as controls. RESULTS: Rigidity measured using our instrument had moderate agreement with the MDS-UPDRS and showed differences between therapeutic state, activation conditions, and disease/healthy cohorts. Rigidity gradually worsened over a one-hour period after DBS cessation, but improved more rapidly with DBS resumption. COMPARISON WITH EXISTING METHODS: Previous attempts to quantify rigidity include manual approaches where a clinician is required to manipulate limbs while sensors passively gather information, or large automated instruments to move the wrist or elbow. CONCLUSION: Given its ability to track changes in rigidity due to therapeutic intervention, our technique could have applications where continuous measurement is required or where a suitably qualified rater is absent.

Objective evaluation of bradykinesia in Parkinson's disease using an inexpensive marker-less motion tracking system.

OBJECTIVE: Quantification of bradykinesia (slowness of movement) is crucial for the treatment and monitoring of Parkinson's disease. Subjective observational techniques are the de-facto 'gold standard', but such clinical rating scales suffer from poor sensitivity and inter-rater variability. Although various technologies have been developed for assessing bradykinesia in recent years, most still require considerable expertise and effort to operate. Here we present a novel method to utilize an inexpensive off-the-shelf hand-tracker (Leap Motion) to quantify bradykinesia. APPROACH: Eight participants with Parkinson's disease receiving benefit from deep brain stimulation were recruited for the study. Participants were assessed 'on' and 'off' stimulation, with the 'on' condition repeated to evaluate reliability. Participants performed wrist pronation/supination, hand open/close, and finger-tapping tasks during each condition. Tasks were simultaneously captured by our software and rated by three clinicians. A linear regression model was developed to predict clinical scores and its performance was assessed with leave-one-subject-out cross validation. MAIN RESULTS: Aggregate bradykinesia scores predicted by our method were in strong agreement (R = 0.86) with clinical scores. The model was able to differentiate therapeutic states and comparison between the test-retest conditions yielded no significant difference (p  = 0.50). SIGNIFICANCE: These findings demonstrate that our method can objectively quantify bradykinesia in agreement with clinical observation and provide reliable measurements over time. The hardware is readily accessible, requiring only a modest computer and our software to perform assessments, thus making it suitable for both clinic- and home-based symptom tracking.

Balance control systems in Parkinson's disease and the impact of pedunculopontine area stimulation.

Impaired balance is a major contributor to falls and diminished quality of life in Parkinson's disease, yet the pathophysiology is poorly understood. Here, we assessed if patients with Parkinson's disease and severe clinical balance impairment have deficits in the intermittent and continuous control systems proposed to maintain upright stance, and furthermore, whether such deficits are potentially reversible, with the experimental therapy of pedunculopontine nucleus deep brain stimulation. Two subject groups were assessed: (i) 13 patients with Parkinson's disease and severe clinical balance impairment, implanted with pedunculopontine nucleus deep brain stimulators; and (ii) 13 healthy control subjects. Patients were assessed in the OFF medication state and blinded to two conditions; off and on pedunculopontine nucleus stimulation. Postural sway data (deviations in centre of pressure) were collected during quiet stance using posturography. Intermittent control of sway was assessed by calculating the frequency of intermittent switching behaviour (discontinuities), derived using a wavelet-based transformation of the sway time series. Continuous control of sway was assessed with a proportional-integral-derivative (PID) controller model using ballistic reaction time as a measure of feedback delay. Clinical balance impairment was assessed using the 'pull test' to rate postural reflexes and by rating attempts to arise from sitting to standing. Patients with Parkinson's disease demonstrated reduced intermittent switching of postural sway compared with healthy controls. Patients also had abnormal feedback gains in postural sway according to the PID model. Pedunculopontine nucleus stimulation improved intermittent switching of postural sway, feedback gains in the PID model and clinical balance impairment. Clinical balance impairment correlated with intermittent switching of postural sway (rho = - 0.705, P < 0.001) and feedback gains in the PID model (rho = 0.619, P = 0.011). These results suggest that dysfunctional intermittent and continuous control systems may contribute to the pathophysiology of clinical balance impairment in Parkinson's disease. Clinical balance impairment and their related control system deficits are potentially reversible, as demonstrated by their improvement with pedunculopontine nucleus deep brain stimulation.

Clinical validation of a precision electromagnetic tremor measurement system in participants receiving deep brain stimulation for essential tremor.

Tremor is characterized commonly through subjective clinical rating scales. Accelerometer-based techniques for objective tremor measurement have been developed in the past, yet these measures are usually presented as an unintuitive dimensionless index without measurement units. Here we have developed a tool (TREMBAL) to provide quantifiable and objective measures of tremor severity using electromagnetic motion tracking. We aimed to compare TREMBAL's objective measures with clinical tremor ratings and determine the test-retest reliability of our technique. Eight participants with ET receiving deep brain stimulation (DBS) therapy were consented. Tremor was simultaneously recorded using TREMBAL and video during DBS adjustment. After each adjustment, participants performed a hands-outstretched task (for postural tremor) and a finger-nose task (for kinetic tremor). Video recordings were de-identified, randomized, and shown to a panel of movement disorder specialists to obtain their ratings. Regression analysis and Pearson's correlations were used to determine agreement between datasets. Subsets of the trial were repeated to assess test-retest reliability. Tremor amplitude and velocity measures were in close agreement with mean clinical ratings (r > 0.90) for both postural and kinetic tremors. Test-retest reliability for both translational and rotational components of tremor showed intra-class correlations >0.80. TREMBAL assessments showed that tremor gradually improved with increasing DBS therapy-this was also supported by clinical observation. TREMBAL measurements are a sensitive, objective and reliable assessment of tremor severity. This tool may have application in clinical trials and in aiding automated optimization of deep brain stimulation.

The relationship between specific cognitive defects and burden of care in Parkinson's disease.

BACKGROUND: In spite of the recognized physical and psychosocial effects of caring for patients with Parkinson's disease (PD), caregiver burden (CB) in this setting is poorly understood. The objective of this research was to identify factors that were associated with CB in an Australian population of PD caregivers using a novel instrument - the Parkinson's Disease Caregiver Burden (PDCB) questionnaire. METHODS: Fifty patient-caregiver couples were recruited from three movement disorders clinics in Melbourne, Australia. Burden on caregivers was rated using the PDCB questionnaire. Burden scores were correlated with patient factors, including motor symptom severity (Unified Parkinson's Disease Ratings Scale and Hoehn & Yahr (H&Y) scale), patient cognition (Neuropsychiatry Unit Cognitive Assessment Tool; NUCOG), presence of impulsive and compulsive behaviors (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease), and patient olfaction. Caregiver and patient demographics, as well as results for depression and anxiety (Hospital Anxiety and Depression Scale; HADS), were also examined for their relationship with CB. RESULTS: H&Y stage, depression or anxiety in either caregiver or patient, and decreased patient NUCOG score were significantly associated with higher PDCB score. Multiple linear regression analysis identified caregiver and patient depression score and patient score for the visuoconstructional subscale of NUCOG to predict burden score. In addition, disease duration, duration of caregiving, and increased hours per day spent in giving care were significantly associated with increased burden. CONCLUSIONS: We found psychiatric and cognitive factors to be the most relevant factors in the perception of burden in PD caregivers. On top of this, we found deficits in the domain of visuoconstruction predicted burden - a relationship not yet described in literature. Targeting depression and anxiety in this setting as well as identifying caregivers at high risk of burden may give clinicians the chance to optimize care of patients with PD through the caregiver.

The Feasibility of Using Acoustic Markers of Speech for Optimizing Patient Outcomes during Randomized Amplitude Variation in Deep Brain Stimulation: A Proof of Principle Methods Study.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for reducing symptoms of tremor. A common and typically subjectively determined adverse effect of DBS is dysarthria. Current assessment protocols are driven by the qualitative judgments of treating clinicians and lack the sensitivity and objectivity required to optimize patient outcomes where multiple stimulation parameters are trialed. OBJECTIVE: To examine the effect of DBS on speech in patients receiving stimulation to the posterior sub-thalamic area (PSA) via randomized manipulation of amplitude parameters. METHODS: Six patients diagnosed with tremor receiving treatment via DBS of the PSA were assessed in a double-blinded, within-subjects experimental protocol. Amplitude (i.e., voltage or current) was randomly adjusted across 10 settings, while speech samples (e.g., sustained vowel, counting to 10) were recorded to identify the patient-specific settings required for optimal therapeutic benefit (reduced tremor) with minimal adverse effects (altered speech). Speech production between stimulation parameters was quantified using acoustic analysis. RESULTS: Speech changed as a response to DBS but those changes were not uniform across patients nor were they generally in line with changes in amplitude with the exception of reduced vocal control and increased mean silence length in two patients. Speech outcomes did not correlate with changes in tremor. CONCLUSION: Intra-individual changes in speech were detected as a response to modified amplitude; however, no clear pattern was observed across patients as a group. The use of objective acoustic measures allows for quantification of speech changes during DBS optimization protocols, even when those changes are subtle and potentially difficult to detect perceptually.

Validity and reliability of the PDCB: a tool for the assessment of caregiver burden in Parkinson's disease.

BACKGROUND: Existing instruments for caregiver burden assessment are not specific or sensitive to various aspects of caring for patients with Parkinson's disease. A better understanding of burden may enhance patient care and improve health of both patient and caregiver. The goal of this study was to evaluate the validity of the Parkinson's Disease Caregiver Burden (PDCB) questionnaire, a novel instrument designed to appraise more accurately the burden experienced by caregivers in the setting of Parkinson's disease. METHODS: Common sources of distress for caregivers were taken from discussions with Parkinson's disease patients, caregivers, and clinicians, and used as the foundation of the PDCB questionnaire items. Fifty patients and their respective caregivers were recruited from three specialist movement disorder clinics. Caregiver burden in the sample was gauged with the PDCB scale and the Caregiver Burden Inventory (CBI). Item sensitivity and questionnaire validity were assessed. RESULTS: In this pilot analysis, the PDCB questionnaire was found to be feasible and reliable. Strong correlations were found between the PDCB questionnaire and the CBI. The PDCB questionnaire contained more relevant items for this population compared with the CBI. CONCLUSION: Strong initial feasibility, reliability, validity, and sensitivity for the PDCB questionnaire were demonstrated. With further evaluation and development, the PDCB questionnaire may prove to be a valuable supplementary tool to the existing CBI or a standalone instrument for use in the setting of Parkinson's disease.

Deep brain stimulation for Parkinson's disease: Australian referral guidelines.

The advent of deep brain stimulation (DBS) has been an important advance in the treatment of Parkinson's disease (PD). DBS may be employed in the management of medication-refractory tremor or treatment-related motor complications, and may benefit between 4.5% and 20% of patients at some stage of their disease course. In Australia, patients with PD are reviewed by specialised DBS teams who assess the likely benefits and risks associated with DBS for each individual. The aim of these guidelines is to assist neurologists and general physicians identify patients who may benefit from referral to a DBS team. Common indications for referral are motor fluctuations and/or dyskinesias that are not adequately controlled with optimised medical therapy, medication-refractory tremor, and intolerance to medical therapy. Early referral for consideration of DBS is recommended as soon as optimised medical therapy fails to offer satisfactory motor control.

Dopamine dysregulation syndrome, impulse control disorders and punding after deep brain stimulation surgery for Parkinson's disease.

Data regarding the effect of deep brain stimulation (DBS) surgery on the dopamine dysregulation syndrome (DDS), impulse control disorders (ICDs) and punding in Parkinson's disease (PD) are limited. We present a case series of 21 operated PD patients who had exhibited DDS, ICDs or punding at some stage during the disease. DDS remained unimproved or worsened post-operatively in 12/17 patients with pre-operative DDS (71%) (nine bilateral subthalamic nucleus [STN], one right-sided STN, two bilateral globus pallidus internus [GPi] DBS). DDS improved or resolved after bilateral STN DBS in 5/17 patients with pre-operative DDS. DDS apparently developed for the first time after bilateral STN DBS in two patients, although only after a latency of eight years in one case. One patient without reported pre-operative DDS or ICDs developed pathological gambling post-STN DBS. One patient had pathological gambling which resolved pre-operatively, and did not recur post-DBS. Thus, DDS, ICDs and punding may persist, worsen or develop for the first time after DBS surgery, although a minority of patients improved dramatically. Predictive factors may include physician vigilance, motor outcome and patient compliance.

Unilateral pallidotomy for Parkinson's disease disrupts ocular fixation.

Although some motor functions of the basal ganglia have been well studied, the oculomotor functions are not well established. We studied eye movements in patients with Parkinson's disease (PD) undergoing pallidotomy to assess the role of the globus pallidus interna (GPi) in oculomotor control. Horizontal visually guided, gap and predictive saccades as well as ocular fixation were studied in patients with advanced PD before and 1 month after unilateral pallidotomy, and in healthy controls on two occasions 1 month apart. There was no difference in saccadic latency or accuracy, the number of saccadic anticipations or the ability to generate predictive saccades between the two assessments for either patients or controls. The number and amplitude of square wave jerks during ocular fixation however increased significantly in patients after pallidotomy. The results imply altered function of frontal or prefrontal cortical regions involved in ocular fixation resulting from a disruption to inhibitory pallidal influences on thalamocortical projections. The posteroventral GPi however appears not to be involved in externally controlled or predictive saccadic function.